Emergence of the natural history of Myhre syndrome: 47 patients evaluated in the Massachusetts General Hospital Myhre Syndrome Clinic (2016-2023).

Myhre syndrome is an increasingly diagnosed ultrarare condition caused by recurrent germline autosomal dominant de novo variants in SMAD4. Detailed multispecialty evaluations performed at the Massachusetts General Hospital (MGH) Myhre Syndrome Clinic (2016-2023) and by collaborating specialists have facilitated deep phenotyping, genotyping and natural history analysis. Of 47 patients (four previously reported), most (81%) patients returned to MGH at least once. For patients followed for at least 5 years, symptom progression was observed in all. 55% were female and 9% were older than 18 years at diagnosis. Pathogenic variants in SMAD4 involved protein residues p.Ile500Val (49%), p.Ile500Thr (11%), p.Ile500Leu (2%), and p.Arg496Cys (38%). Individuals with the SMAD4 variant p.Arg496Cys were less likely to have hearing loss, growth restriction, and aortic hypoplasia than the other variant groups. Those with the p.Ile500Thr variant had moderate/severe aortic hypoplasia in three patients (60%), however, the small number (n = 5) prevented statistical comparison with the other variants. Two deaths reported in this cohort involved complex cardiovascular disease and airway stenosis, respectively. We provide a foundation for ongoing natural history studies and emphasize the need for evidence-based guidelines in anticipation of disease-specific therapies.

Adverse events rates and risk factors in adults undergoing cardiac catheterization at pediatric hospitals--results from the C3PO.

OBJECTIVE: Determine the frequency and risk factors for adverse events (AE) for adults undergoing cardiac catheterization at pediatric hospitals. BACKGROUND: Adult catheterization AE rates at pediatric hospitals are not well understood. The Congenital Cardiac Catheterization Project on Outcomes (C3PO) collects data on all catheterizations at eight pediatric institutions. METHODS: Adult (≥ 18 years) case characteristics and AE were reviewed and compared with those of pediatric (<18 years) cases. Cases were classified into procedure risk categories from 1 to 4 based on highest risk procedure/intervention performed. AE were categorized by level of severity. Using a multivariate model for high severity AE (HSAE), standardized AE rates (SAER) were calculated by dividing the observed rates of HSAE by the expected rates. RESULTS: 2,061 cases (15% of total) were performed on adults and 11,422 cases (85%) were performed on children. Adults less frequently underwent high-risk procedure category cases than children (19% vs. 30%). AE occurred in 10% of adult cases and 13% of pediatric cases (P < 0.001). HSAE occurred in 4% of adult and 5% of pediatric cases (P = 0.006). Procedure-type risk category (Category 2, 3, 4 OR = 4.8, 6.0, 12.9) and systemic ventricle end diastolic pressure ≥ 18 mm Hg (OR 3.1) were associated with HSAE, c statistic 0.751. There were no statistically significant differences in SAER among institutions. CONCLUSIONS: Adults undergoing catheterization at pediatric hospitals encountered AE less frequently than children did. The congenital heart disease adjustment for risk method for adults with congenital heart disease is a new tool for assessing procedural risk in adult patients.

Tissue Doppler measurements correlate with central venous pressure in pediatric patients after cardiac surgery.

Tissue Doppler imaging (TDI) measurements have been demonstrated to correlate with central venous pressure (CVP) in adults. We hypothesize that TDI measurements also correlate with CVP in children after cardiac surgery. Patients younger than 10 years with invasive CVP monitoring after cardiac surgery were studied. Annular tissue and atrioventricular inflow velocities were measured daily during CVP monitoring. Tissue Doppler imaging measurements were compared with CVP by univariate analyses. Subgroup analyses were performed for univentricular versus biventricular hearts. p values < or = 0.05 were considered significant. Fifty studies were performed on 28 subjects; 20 studies were performed on patients with univentricular physiology; and 30 studies were performed on patients with biventricular physiology. For all subjects, CVP correlated significantly with the right ventricular TDI measurements of e' velocity (r = -0.43), a' velocity (r = 0.35), e'/a' ratio (r = -0.42), and E/e' ratio (r = 0.44). For biventricular patients, e' velocity (r = -0.35), e'/a' ratio (r = -0.38), and E/e' ratio (r = 0.58) correlated significantly. For univentricular patients, E velocity (r = -0.62), e' velocity (r = -0.50), and a' (r = 0.61) velocity correlated significantly. Tissue Doppler imaging measurements of the right heart significantly correlated with invasively measured CVP in pediatric subjects. Different measures may correlate more strongly in those with biventricular versus univentricular physiology. With additional study, TDI may prove a valid tool for noninvasively assessing CVP in children with both bi- and univentricular physiology.